Cancer Research and Treatment

Original Article

The Increasing Frequency of Cervical Cancer in Korean Women under 35: Chan Hee Han, Hyun Jung Cho, Sung Jong Lee, Jeong Hoon Bae, Seog Nyen Bae, Sung Eun Namkoong, Jong Sup Park; Cancer Res Treat. 2008;40(1):1-5. Published online March 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.1.1

Purpose

The goal of this study was to determine the clinical and epidemiological trends of cervical cancer in young Korean women. Social behavior including sexual habits has changed in Korean women, with sexual activity commencing at a younger age. These changes are likely to influence certain risk factors of cervical cancer, resulting in changing trends in the occurrence of the disease.

Materials and Methods

The incidence of cervical cancer in women less than 35 years-old between January 1990 and December 2006 was analyzed, and available medical records from January 1996 to December 2006 were reviewed. The clinical, pathological and epidemiologic characteristics and changing trends among these young patients were analyzed.

Results

Over the last two decades, the incidence of young (< 35 years) cervical cancer patients increased, more patients had an aggressive form of the disease, and there was a higher rate of women with more advanced education. Human papillomavirus (HPV) infection was detected in 94.0% of the women (63/67) tested. HPV 16 (82.5%) and HPV 18 (12.7%) were the two most common viral infections detected throughout the study period.

Conclusions

The changing trends and risk factors identified suggest a need for more active education of young women about cervical cancer prevention strategies. In addition, young women are strongly recommended to undergo a regular screening test and HPV vaccination.

Citations

Citations to this article as recorded by

Prevalence and Treatment of Vulvar Cancer From 2014−2018: A Nationwide Population-Based Study in Korea
Yung-Taek Ouh, Dongwoo Kang, Hoseob Kim, Jae Kwan Lee, Jin Hwa Hong
Journal of Korean Medical Science.2022;[Epub] CrossRef
Successful Treatment of Synchronous Double Lung Primary Malignancies and Colon Cancer
Hosam A Alghanmi
Cureus.2022;[Epub] CrossRef
WITHDRAWN: Polymerase chain reaction technique for molecular detection of HPV16 infections among women with cervical cancer in Dhi-Qar Province
Abduladheem Turki Jalil, Ali Hussein Demin Al-Khafaji, Aleksandr Karevskiy, Saja Hussain Dilfy, Zaman K. Hanan
Materials Today: Proceedings.2021;[Epub] CrossRef
Current Status of Human Papillomavirus Infection and Introduction of Vaccination to the National Immunization Program in Korea: an Overview
Min-A Kim, Gwan Hee Han, Jae-Hoon Kim, Kyung Seo
Journal of Korean Medical Science.2018;[Epub] CrossRef
Management for locally advanced cervical cancer: new trends and controversial issues
Oyeon Cho, Mison Chun
Radiation Oncology Journal.2018; 36(4): 254. CrossRef
Trends and Age-Period-Cohort Effects on the Incidence and Mortality Rate of Cervical Cancer in Korea
Eun-Kyeong Moon, Chang-Mo Oh, Young-Joo Won, Jong-Keun Lee, Kyu-Won Jung, Hyunsoon Cho, Jae Kwan Jun, Myong Cheol Lim, Moran Ki
Cancer Research and Treatment.2017; 49(2): 526. CrossRef
Factors associated with participation in cervical cancer screening among young Koreans: a nationwide cross-sectional study
Ha Kyun Chang, Jun-Pyo Myong, Seung Won Byun, Sung-Jong Lee, Yong Seok Lee, Hae-Nam Lee, Keun Ho Lee, Dong Choon Park, Chan Joo Kim, Soo Young Hur, Jong Sup Park, Tae Chul Park
BMJ Open.2017; 7(4): e013868. CrossRef
Molecular Detection and Typing of Human Papillomaviruses in Paraffin-Embedded Cervical Cancer and Pre-Cancer Tissue Specimens
Pezhman Mahmoodi, Hossein Motamedi, Masoud Reza Seyfi Abad Shapouri, Mahjabin Bahrami Shehni, Mohammad Kargar
Iranian Journal of Cancer Prevention.2016;[Epub] CrossRef
Cervical cancer in north-eastern Libya: 2000–2008
F. Ben Khaial, Z. Bodalal, A. Elramli, F. Elkhwsky, A. Eltaguri, R. Bendardaf
Journal of Obstetrics and Gynaecology.2014; 34(6): 523. CrossRef
Current status of the National Cancer Screening Program for cervical cancer in Korea, 2009
Young Hwa Lee, Kui Son Choi, Hoo-Yeon Lee, Jae Kwan Jun
Journal of Gynecologic Oncology.2012; 23(1): 16. CrossRef
Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study
J.-H. Nam, J.-Y. Park, D.-Y. Kim, J.-H. Kim, Y.-M. Kim, Y.-T. Kim
Annals of Oncology.2012; 23(4): 903. CrossRef
The safety of conization in the management of adenocarcinomain situof the uterine cervix
Mi-La Kim, Ho-Suap Hahn, Kyung-Taek Lim, Ki-Heon Lee, Hy-Sook Kim, Sung-Ran Hong, Tae-Jin Kim
Journal of Gynecologic Oncology.2011; 22(1): 25. CrossRef
Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women
Seung Cheol Kim, Yong Sang Song, Young-Tae Kim, Young Tak Kim, Ki-Sung Ryu, Bhavyashree Gunapalaiah, Dan Bi, Hans L Bock, Jong-Sup Park
Journal of Gynecologic Oncology.2011; 22(2): 67. CrossRef
Prognostic value of metabolic tumor volume measured by FDG-PET/CT in patients with cervical cancer
Hyun Hoon Chung, Jae Weon Kim, Kyung Hee Han, Jae Seon Eo, Keon Wook Kang, Noh-Hyun Park, Yong-Sang Song, June-Key Chung, Soon-Beom Kang
Gynecologic Oncology.2011; 120(2): 270. CrossRef

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Retraction

Retraction: Comparison of As2O3 and As4O6 in the Detection of SiHa Cervical Cancer Cell G rowth Inhibition Pathway: Yong Wook Kim, Su Mi Bae, Keun Ho Lee, Joon Mo Lee, Sung Eun Namkoong, Insu P. Lee, Chong Kook Kim, Jeong-Sun Seo, Jeong-Im Sin, Yong-Wan Kim, Woong Shick Ahn; Cancer Res Treat. 2007;39(1):47-47. Published online March 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.1.47; Retracts: Cancer Res Treat 2004;36(4):255

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Original Articles

Activity of Green Tea Polyphenol Epigallocatechin-3-gallate Against Ovarian Carcinoma Cell Lines: Yong Wook Kim, Su Mi Bae, Joon Mo Lee, Sung Eun Namkoong, Sei Jun Han, Byoung Rai Lee, Insu P. Lee, Sang Hee Kim, Young Joo Lee, Chong Kook Kim, Yong-Wan Kim, Woong Shick Ahn; Cancer Res Treat. 2004;36(5):315-323. Published online October 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.5.315

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Purpose

A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), is known to possess anti-cancer properties. In this study, the time-course of the anticancer effects of EGCG on human ovarian cancer cells were investigated to provide insights into the molecular-level understanding of the growth suppression mechanism involved in EGCG-mediated apoptosis and cell cycle arrest.

Materials and Methods

Three human ovarian cancer cell lines (p53 negative, SKOV-3 cells; mutant type p53, OVCAR-3 cells; and wild type p53, PA-1 cells) were used. The effect of EGCG treatment was studied via a cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay.

Results

EGCG exerts a significant role in suppressing ovarian cancer cell growth, showed dose dependent growth inhibitory effects in each cell line and induced apoptosis and cell cycle arrest. The cell cycle was arrested at the G1 phase by EGCG in SKOV-3 and OVCAR-3 cells.

In contrast, the cell cycle was arrested in the G1/S phase in PA-1 cells. EGCG differentially regulated the expression of genes and proteins (Bax, p21, Retinoblastoma, cyclin D1, CDK4 and Bcl-X_L) more than 2 fold, showing a possible gene regulatory role for EGCG. The continual expression in p21WAF1 suggests that EGCG acts in the same way with p53 proteins to facilitate apoptosis after EGCG treatment. Bax, PCNA and Bcl-X are also important in EGCG-mediated apoptosis. In contrast, CDK4 and Rb are not important in ovarian cancer cell growth inhibition.

Conclusion

EGCG can inhibit ovarian cancer cell growth through the induction of apoptosis and cell cycle arrest, as well as in the regulation of cell cycle related proteins. Therefore, EGCG-mediated apoptosis could be applied to an advanced strategy in the development of a potential drug against ovarian cancer.

Citations

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Role of Epigallocatechin Gallate in Selected Malignant Neoplasms in Women
Anna Markowska, Michał Antoszczak, Janina Markowska, Adam Huczyński
Nutrients.2025; 17(2): 212. CrossRef
Epigallocatechin 3-gallate: From green tea to cancer therapeutics
Manzar Alam, Sabeeha Ali, Ghulam Md. Ashraf, Anwar L. Bilgrami, Dharmendra Kumar Yadav, Md. Imtaiyaz Hassan
Food Chemistry.2022; 379: 132135. CrossRef
Synergistic effects of green tea extract and paclitaxel in the induction of mitochondrial apoptosis in ovarian cancer cell lines
Mohammad Panji, Vahideh Behmard, Zahra Zare, Monireh Malekpour, Hasan Nejadbiglari, Saeede Yavari, Tina Nayerpour dizaj, Azadeh Safaeian, Ali Bakhshi, Omid Abazari, Mojtaba Abbasi, Parisa Khanicheragh, Maryam Shabanzadeh
Gene.2021; 787: 145638. CrossRef
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Ana Margarida Teixeira, Clara Sousa
Molecules.2021; 26(8): 2178. CrossRef
Estrogenic biological activity and underlying molecular mechanisms of green tea constituents
Ryoiti Kiyama
Trends in Food Science & Technology.2020; 95: 247. CrossRef
Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells
Rhiane Moody, Kirsty Wilson, Anthony Jaworowski, Magdalena Plebanski
Cancers.2020; 12(3): 673. CrossRef
Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer
Saleh A. Almatroodi, Ahmad Almatroudi, Amjad Ali Khan, Fahad A. Alhumaydhi, Mohammed A. Alsahli, Arshad Husain Rahmani
Molecules.2020; 25(14): 3146. CrossRef
The Potential Roles of Epigallocatechin-3-Gallate in the Treatment of Ovarian Cancer: Current State of Knowledge

Sabrina Bimonte, Marco Cascella
Drug Design, Development and Therapy.2020; Volume 14: 4245. CrossRef
Bioinformatics Analysis on Molecular Mechanism of Green Tea Compound Epigallocatechin‐3‐Gallate Against Ovarian Cancer
S Xinqiang, Z Mu, C Lei, LY Mun
Clinical and Translational Science.2017; 10(4): 302. CrossRef
Pharmacological profile of green tea and its polyphenols: a review
Sumit Bansal, Navneet Syan, Pooja Mathur, Shivani Choudhary
Medicinal Chemistry Research.2012; 21(11): 3347. CrossRef
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Salvatore Chirumbolo
Journal of the Science of Food and Agriculture.2012; 92(8): 1573. CrossRef
Green tea for ovarian cancer prevention and treatment: A systematic review of the in vitro, in vivo and epidemiological studies
Dominique Trudel, David P. Labbé, Isabelle Bairati, Vincent Fradet, Laurent Bazinet, Bernard Têtu
Gynecologic Oncology.2012; 126(3): 491. CrossRef
Tea Consumption and Epithelial Ovarian Cancer Risk: A Systematic Review of Observational Studies
Sarah J. Oppeneer, Kim Robien
Nutrition and Cancer.2011; 63(6): 817. CrossRef

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Comparison of As₂O₃ and As₄O₆ in the Detection of SiHa Cervical Cancer Cell Growth Inhibition Pathway: Yong Wook Kim, Su Mi Bae, Keun Ho Lee, Joon Mo Lee, Sung Eun Namkoong, Insu P. Lee, Chong Kook Kim, Jeong-Sun Seo, Jeong-Im Sin, Yong-Wan Kim, Woong Shick Ahn; Cancer Res Treat. 2004;36(4):255-262. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.255; Retraction in: Cancer Res Treat 2007;39(1):47

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Expression Profiling of the Cellular Processes in Uterine Leiomyomas: Omic Approaches and IGF-2 Association with Leiomyosarcomas: Su Mi Bae, Yong-Wan Kim, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Woong Shick Ahn; Cancer Res Treat. 2004;36(1):31-42. Published online February 29, 2004; DOI: https://doi.org/10.4143/crt.2004.36.1.31

Abstract PDF PubReader ePub

Purpose

This study utilized both cDNA microarray and 2D protein gel electrophoresis technology to investigate the multiple interactions of the genes and proteins involved in the pathophysiology of uterine leiomyomas. Also, Gene Ontology (GO) analysis was used to systematically characterize the global expression profiles, which were found to correlate with the leiomyosarcomas.

Materials and Methods

The uterine leiomyoma biopsies were obtained from patients in the Department of Obstetrics and Gynecology, The Catholic University of Korea. Differentially expressed transcriptome and proteome, in 6 paired leiomyoma and normal myometrium, were profiled. The total RNAs from the leiomyoma and normal myometrium were labeled with Cy5 and Cy3. All specimens were punch-biopsy-obtained, and frozen in liquid nitrogen.

Results

Screening of up to 17,000 genes identified 71 that were either up-regulated or down-regulated (21 and 50, respectively). The gene expression profiles were classified into 420 mutually dependent functional sets, resulting in 611 cellular processes, according to the gene ontology. Also, the protein analysis, using 2D gel electrophoresis, identified 33 proteins (17 up-regulated and 16 down-regulated) with more than 500 total spots, which were classified into 302 cellular processes. O f these functional profilings, transcriptomes and proteoms down-regulations were shown in the cell adhesion, cell m otility, organogenesis, enzyme regulator, structural molecule activity and responses to external stimulus functional activities, which are supposed to play important roles in the pathophysiology. In contrast, up-regulation was only shown in the nucleic acid binding activity. The CDKN2A, ADH1A, DCX, IGF2, CRABP2 and KIF5C were found to increase the reliability of this study, and correlate with the leiomyosarcomas.

Conclusion

Potentially significant pathogenetic cellular processes showed that down-regulated functional profiling has an important impact on the discovery of the pathogenic pathways in leiomyomas and leiomyosarcomas. GO analysis can also overcome the complexity of the expression profiles of cDNA microarrays and 2D protein analyses, via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at cellular process levels.

Citations

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H3K4me3 mediates uterine leiomyoma pathogenesis via neuronal processes, synapsis components, proliferation, and Wnt/β-catenin and TGF-β pathways
María Cristina Carbajo-García, Elena Juarez-Barber, Marina Segura-Benítez, Amparo Faus, Alexandra Trelis, Javier Monleón, Greta Carmona-Antoñanzas, Antonio Pellicer, James M. Flanagan, Hortensia Ferrero
Reproductive Biology and Endocrinology.2023;[Epub] CrossRef
Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas
Tsai-Der Chuang, Jianjun Gao, Derek Quintanilla, Hayden McSwiggin, Drake Boos, Wei Yan, Omid Khorram
International Journal of Molecular Sciences.2023; 24(4): 3742. CrossRef
Analysis of JAM-A T>C (rs790056) and LFA-1 2120 G>C (rs2230433) gene variations in uterine leiomyoma
Özge KÖMÜRCÜ KARUSERCİ, Esra GÜZEL TANOĞLU, Halime Hanım PENÇE, Mete Gürol UĞUR
Anatolian Current Medical Journal.2021; 3(1): 48. CrossRef
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Leiomyosarcoma: A rare soft tissue cancer arising from multiple organs
Zorawar Singh
Journal of Cancer Research and Practice.2018; 5(1): 1. CrossRef
Integrated analysis reveals candidate mRNA and their potential roles in uterine leiomyomas
Liping Xia, Yan Liu, Yan Fu, Shengyi Dongye, Dewei Wang
Journal of Obstetrics and Gynaecology Research.2017; 43(1): 149. CrossRef
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Qiong Zou, Zhulin Yang, Daiqiang Li, Ziru Liu, Yuan yuan
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Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis
BLENDI URA, FEDERICA SCRIMIN, FABRIZIO ZANCONATI, GIORGIO ARRIGONI, LORENZO MONASTA, ANDREA ROMANO, RUBINA BANCO, MARINA ZWEYER, DANIELA MILANI, GIUSEPPE RICCI
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Photogem Induces Necrosis in Various Uterine Cervical Cancer Cell Lines by PDT: Su Mi Bae, Seung Won Huh, Eun Kyung Park, Keun Ho Lee, Joon Mo Lee, Sung Eun Namkoong, Sei Jun Han, Chong Kook Kim, Jong Ki Kim, Yong Wan Kim, Woong Shick Ahn; Cancer Res Treat. 2003;35(6):549-556. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.549

Abstract PDF

PURPOSE
In order to elucidate the antitumor effect of photodynamic therapy (PDT), using a derivative of the photosensitizing agent hematoporphyrin (Photogem) and a diode laser, the cell death of uterine cancer cell lines (CaSki, HT3, HeLa, and SKOV-3), and mice transplanted with TC-1 lung cancer cells, were evaluated. MATERIALS AND METHODS: The morphological changes, MTT assay, flow cytometry, cytotoxicity and tumor growth inhibition study were evaluated at various time intervals after the PDT.
RESULTS
The results showed that the survival rates of each cell line decreased with time and dose response after performing the PDT. Also, the PDT-induced damage of cancer cells was almost entirely confined to necrosis of the tumor cells in the early time courses. The irradiation of CaSki cells in the presence of Photogem induced plasma membrane disruption and cell shrinkage, indicating the plasma membrane as the main target for Photogem. In the in vivo experiment, significantly longer survival and a significantly smaller tumor size were seen over the time courses of the Photogem with irradiation compared to the untreated control groups; resorption of the tumor was also observed after the PDT treatment. CONCLUSION: Collectively, our results indicated that Photogem possesses anti-tumor effects, and necrosis-like death, with plasma membrane damage, was postulated to be the principal mechanism of the antitumor effect of the PDT using Photogem.

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Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells
Lan Ying Wen, Su-Mi Bae, Heung-Jae Chun, Kye-Shin Park, Woong Shick Ahn
Lasers in Medical Science.2012; 27(2): 445. CrossRef
Shift from Apoptotic to Necrotic Cell Death during Human Papillomavirus-induced Transformation of Keratinocytes
Nataly Kravchenko-Balasha, Sarit Mizrachy-Schwartz, Shoshana Klein, Alexander Levitzki
Journal of Biological Chemistry.2009; 284(17): 11717. CrossRef
Photodynamic Effects of Radachlorin® on Cervical Cancer Cells
Su-Mi Bae, Yong-Wook Kim, Joon-Mo Lee, Sung-Eun Namkoong, Sei-Jun Han, Jong-Ki Kim, Chang-Hee Lee, Heung-Jae Chun, Hyun-Sun Jin, Woong-Shick Ahn
Cancer Research and Treatment.2004; 36(6): 389. CrossRef

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cDNA Microarray Analysis of Gene Expression Profiles Associated with Cervical Cancer: Joo Hee Yoon, Joon Mo Lee, Sung Eun Namkoong, Su Mi Bae, Yong Wan Kim, Sei Jun Han, Young Lae Cho, Gye Hyun Nam, Chong Kook Kim, Jeong Sun Seo, Woong Shick Ahn; Cancer Res Treat. 2003;35(5):451-459. Published online October 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.5.451

Abstract PDF

PURPOSE
The molecular pathology of cervical cancers associated with human papillomavirus infection is presently unclear. In an effort to clarify this issue, the gene expression profiles and pathogenic cellular processes of cervical cancer lesions were investigated. MATERIALS AND METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The tissue samples of 11 patients (invasive cancer stage Ib- IIIa) were investigated by a cDNA microarray of 4, 700 genes, hierarchical clustering and the Gene Ontology (GO). Total RNA from cervical cancer and non-lesional tissues were labeled with Cy5 and Cy3. The HaCaT human epithelial keratinocyte cell line was used as a negative control cell. The stages of invasive cancer were Ib to IIIb. All specimens were obtained by punch-biopsies and frozen in liquid nitrogen until required. RESULTS: 74 genes, showing more than a 2 fold difference in their expressions, were identified in at least 8 of the 11 patients. Of these genes, 33 were up-regulated and 41 were down-regulated. The gene expression profiles were classified into 345 mutually dependent function sets, resulting in 611 cellular processes according to their GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis and nucleic acid metabolism. The genes related to nucleic acid binding and structural molecule activity were also significantly down-regulated. In contrast, significant up-regulation was shown in the skeletal development, immune response and extracellular activity. CONCLUSION: These data are suggestive of potentially significant pathogenetic cellular processes, and showed that the down-regulated functional profiling has an important impact on the discovery of pathogenic pathways in cervical carcinogenesis. GO analysis can also overcome the complexity of the expression profiles of the cDNA microarray via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at the cellular process levels.

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Altered MicroRNA Expression in Cervical Carcinomas
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Clinical Cancer Research.2008; 14(9): 2535. CrossRef
Identification of hemoglobin‐α and ‐β subunits as potential serum biomarkers for the diagnosis and prognosis of ovarian cancer
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Cancer Research and Treatment.2004; 36(1): 43. CrossRef

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New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology: Yong Wan Kim, Min Je Suh, Jin Sik Bae, Su Mi Bae, Joo Hee Yoon, Soo Young Hur, Jae Hoon Kim, Duck Young Ro, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Woong Shick Ahn; Cancer Res Treat. 2003;35(4):304-313. Published online August 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.4.304

Abstract PDF

No abstract available.

Citations

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BAG3 down-modulation sensitizes HPV18+ HeLa cells to PEITC-induced apoptosis and restores p53
Roberta Cotugno, Anna Basile, Elena Romano, Dario Gallotta, Maria Antonietta Belisario
Cancer Letters.2014; 354(2): 263. CrossRef
Expression Profiling of the Cellular Processes in Uterine Leiomyomas: Omic Approaches and IGF-2 Association with Leiomyosarcomas
Su Mi Bae, Yong-Wan Kim, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Woong Shick Ahn
Cancer Research and Treatment.2004; 36(1): 31. CrossRef

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Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recombinant Adenovirus p53 in vitro and in vivo: Su Mi Bae, Yong Wook Kim, Joo Hee Yoon, Jin Young Yoo, Young Seok Seo, Sang Lyun Nam, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Yong Wan Kim, Woong Shick Ahn; Cancer Res Treat. 2003;35(3):181-190. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.181

Abstract PDF

PURPOSE
Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell-specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. MATERIALS AND METHODS: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. RESULTS: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3 On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa. The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns.
CONCLUSION
The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line.

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Immunization with Adenoviral Vectors Carrying Recombinant IL-12 and E7 Enhanced the Antitumor Immunity against Human Papillomavirus 16-associated Tumor
Eun-Kyung Park, Young-Wook Kim, Joon-Mo Lee, Sung-Eun NamKoong, Do-Gang Kim, Heung-Jae Chun, Byoung-Don Han, Su-Mi Bae, Hyun-Sun Jin, Jeong-Im Sin, Woong-Shick Ahn
Cancer Research and Treatment.2005; 37(1): 63. CrossRef

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Polymorphisms of p53, p21 and IRF-1 and Cervical Cancer Susceptibility in Korean Women: Sung Jong Lee, Sung Eun Namkoong, Won Chul Lee, Jae Woong Sul, Sun Ha Jee, Youn Kyoung You, Jong Eun Lee, Jong Sup Park; Cancer Res Treat. 2002;34(5):357-364. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.357

Abstract PDF

PURPOSE
The aim of this study was to identify gene- gene and gene-environmental factor on cervical carcinogenesis in Korean women.
MATERIALS AND METHODS
We evaluated 185 women patients who had cervical cancer with 345 normal control healthy women. The single nucleotide polymorphisms (SNPs) of the p53 codon 72, the p21 codon 31 and the IRF-1 intron 6 were evaluated from extracted DNA of peripheral blood with an automatic DNA sequencer. The difference of each SNP, gene-gene and gene-environmental interaction between normal controls and patients, were evaluated in an adjusted environmental background.
RESULTS
With regard to environmental factors, the cervical cancer increased in the women with a lower level of education, a younger age at first sexual intercourse and with the increased number of children borne. The women who had p53 (Arg/Arg), IRF-1 (T/T) and an education of less than 6 years showed a 14.7 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and an education of more than 15 years. The women who had p53 (Arg/Arg), p21 (Ser/Ser) and more than 3 children showed a 6.4 fold increased risk of cervical cancer than those women who had p53 (~Pro), p21 (~Arg) and had borne no child. The women who had p53 (Arg/Arg), IRF-1 (T/T) and had experience of first sexual intercourse before the age of 22-years showed a 5.5 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and had experience of first sexual intercourse after the age of 26-years.
CONCLUSION
We found that the level of education, the age at first intercourse, and the number of children borne, were independent risk factors in cervical carcinogenesis. The specific combination of p53, p21 and IRF-1 gene-gene and gene-environmental interactions were significantly noted in the cervical carcinogenesis of Korean women.

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Distinctive cell cycle regulatory protein profiles by adenovirus delivery of p53 in human papillomavirus-associated cancer cells
H.-S. JIN, S.-M. BAE, Y.-W. KIM, J.-M. LEE, S.-E. NAMKOONG, B.-D. HAN, Y.-J. LEE, C.-K. KIM, H.-J. CHUN, W.-S. AHN
International Journal of Gynecological Cancer.2006; 16(2): 698. CrossRef
Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells
Yong-Seok Lee, Su-Mi Bae, Sun-Young Kwak, Dong-Chun Park, Yong-Wook Kim, Soo-Young Hur, Eun-Kyung Park, Byoung-Don Han, Young-Joo Lee, Chong-Kook Kim, Do Kang Kim, Woong-Shick Ahn
Cancer Research and Treatment.2006; 38(3): 168. CrossRef
Cellular process classification of human papillomavirus-16-positive SiHa cervical carcinoma cell using Gene Ontology
W. S. Ahn, M.-J. Seo, S. M. Bae, J. M. Lee, S. E. Namkoong, C. K. Kim, Y.-W. Kim
International Journal of Gynecological Cancer.2005; 15(1): 94. CrossRef

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Growth Suppression of Ovarian Cancer Cells by Interferon-gama: Jong Sup Park, Eun Joo Kim, Tae Chul Park, Eun Jung Kim, Jin Kim, Joon Mo Lee, Sung Eun Namkoong, Soo Jong Um; Cancer Res Treat. 2001;33(3):236-242. Published online June 30, 2001; DOI: https://doi.org/10.4143/crt.2001.33.3.236

Abstract PDF

PURPOSE
Growth regulation of cancer cells very frequently involves tumor suppressor gene p53, Rb and cell cycle regulator, however the molecular biologic mechanisms of growth regulation in ovarian carcinoma cells are not fully defined. To assess the mechanism of growth suppression, we treated IFN-gama in ovarian carcinoma cells.
MATERIALS AND METHODS
Growth suppression by treatment of IFN-gama was determined by cell proliferation assay in ovarian carcinoma cell lines. Apoptosis was determined by DNA fragmentation assay and electron microscopy. Molecular mechanism of the apoptosis in ovarian carcinoma cell by IFN-gama was further analyzed by the western blot.
RESULTS
We found that IFN-gama had remarkable growth- suppressive effects in PA-1 and A2774 ovarian carcinoma cells in a time-dependent manner. Apoptosis was observed in PA-1 and A2774 cell following treatment of IFN- gama by DNA fragmentation assay and EM. The expression of IRF-1 protein from A2774 and PA-1 cell extracts was elevated by increasing the concentration of IFN-gama. IFN-gama caused an increased expression of the important apoptosis-related gene, ICE (interleukin-1beta-converting enzyme) protein in A2774 and PA-1.
CONCLUSION
The coordinate induction of IRF-1 and ICE by IFN-gama in ovarian carcinoma cells suggests a functional relationship between these proteins in programmed cell death. The significance of this study is the molecular biologic background of IFN-gama considered as an alternative treatment trial of ovarian cancers.

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Cdk2-dependent phosphorylation of the NF-Y transcription factor is essential for the expression of the cell cycle-regulatory genes and cell cycle G1/S and G2/M transitions
Hee-Don Chae, Jeanho Yun, Yung-Jue Bang, Deug Y Shin
Oncogene.2004; 23(23): 4084. CrossRef
Cdk2-dependent Phosphorylation of the NF-Y Transcription Factor and Its Involvement in the p53-p21 Signaling Pathway
Jeanho Yun, Hee-Don Chae, Tae-Saeng Choi, Eun-Hee Kim, Yung-Jue Bang, Jongkyeong Chung, Kyeong-Sook Choi, Roberto Mantovani, Deug Y. Shin
Journal of Biological Chemistry.2003; 278(38): 36966. CrossRef

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Growth Regulation of Ovarian Cancer Cells through the Inactivation of AP-1 by Retinoid Derivatives: Young Me Koh, Jong Sup Park, Sung Eun Namkoong, So Young Lee, Soo A Kim, Kyong Ja Hong, Soo Jong Um; J Korean Cancer Assoc. 2000;32(6):1043-1049.

Abstract PDF: PURPOSE
The growth regulatory effect of retinoid derivatives could be mediated by the transcriptional inactivation of AP-1 oncogenic transcription factor. By using ovarian cancer cell lines we were to investigate the cross-regulation mechanism between retinoids and AP-1.
MATERIALS AND METHODS
Cell proliferation assays were performed in 4 ovarian cancer cells (A2774, PA-1, OVCAR-3, SKOV-3) by increasing the concentrations of all-trans retinoic acid (ATRA), 9-cis retinoic acid (9RA), 13-cis RA (13RA), 4-hydroxyphenyl retinamide (4-HPR). Transient transfection and CAT ELISA were done to determine the selective activity of each retinoid on the RAR (alpha, beta, gamma), RXR (alpha, beta, gamma). and the negative activity on AP-1 (c-Jun).
RESULTS
Antiproliferative effect of 4-HPR (IC50; 0.7~2.7 micrometer) was more potent than those of other retinoid derivatives (IC50; 2.7~9.0 micrometer). To assess the anticancer mechanism, we examined the effect of 4-HPR on the transriptional activity of retinoic acid receptors (RAR/RXR) and of c-jun. Contrary to other retinoid derivatives that are active for RAR and RXR with some different levels, 4-HPR showed weak activity only for RARgamma. However, 4-HPR exerted the strongest suppression on AP-1 (c-Jun) activity.
CONCLUSION
Based on our results showing much 4-HPR's potent antiproliferative activity coupled with the most effectively inhibiting activity on AP-1 and minimum activity on RA receptor (selective for RARgamma) than other retinoid derivatives, we suggest that 4-HPR may be a novel, and very effective anticancer drugs for ovarian cancer.

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Clinical Trial

Potentials of Fractionated Infusions of Low-dose Peripheral Blood Stem Cells (PBSCs) to Overcome the Hematologic Toxocities after Combination Chemotherapy: Seok Goo Cho, Jun Mo Lee, Jin No Park, Hoon Kyo Kim, Sung Eun Namkoong, Kyung Shick Lee, Chun Choo Kim; J Korean Cancer Assoc. 2000;32(5):943-953.

Abstract PDF: PURPOSE
We tried to evaluate the clinical usefullness of fractionated low-dose infusions of peripheral blood stem cells (PBSCs) as a supportive care.
MATERIALS AND METHODS
Four patients were entered onto this study who were diagnosed to have gastric lymphoma (n=1) and advanced ovarian carcinomas (n=3). To overcome the hematologic toxicities, G-CSF-mobilized PBSCs were collected early in disease course. Harvested products were cryopreserved in aliquotes and then infused after each cycle. Planned therapeutic schedules should be performed without changes of dose and interval regardless of hematologic toxicities.
RESULTS
20 cycles of chemotherapies were performed and data of infused cell doses were as follows: median number of PBSCs infusions, 4.5 (3~5); median MNCs, CFU-GM colony counts per infusion of low-dose PBSCs, 1.7 108/kg (1.0~2.4), 3.2 104/kg (2.1~11.8). Among 20 cycles, delayed recovery of thrombocytopenia was shown on 10 cycles. Leukopenia (III/IV) and thrombocytopenia (III/IV) were shown on 8/6 cycles and 8/2 cycles. In spite of myelosuppression, they were successfully treated with planned dose-intensity. Especially incomplete platelet recovery was successfully rescuced by using fractionated infusions of low-dose PBSCs.
CONCLUSION
These data warrant further clinical trials to evaluate the potentials of fractionated low-dose infusions of PBSCs collected early in disease course for overcoming accumulated hematologic toxicities, especially thrombocytopenia complicated by repeated chemotherapies.

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Original Article

The Effects of Interferon/Retinoic Acid on Cervical Cancer Cell Lines According to the Mutational Status of HPV-URR: Tae Yeon Kim, Chan Joo Kim, Eun Joo Kim, Tae Chul Park, Sung Eun Namkoong, Jae Gahb Park, Soo Jong Um, Jong Sup Park; J Korean Cancer Assoc. 2000;32(5):884-894.

Abstract PDF: PURPOSE
We investigated the effects of all-trans-retinoic acid (ATRA) and/or interferon-gamma (IFN-gamma) on the growth of various cervical cancer cell lines and HPV E6/E7 expression. The relationships between the functional activities of HPV-URR and the growth inhibition were identified.
MATERIALS AND METHODS
Four groups of cell lines were included; i) with integrated form of HPV-16 DNA (SNU-17, CaSki), ii) episomal form of HPV-16 (SNU-523), iii) integrated form of HPV-18 (SNU-1160, HeLa) and iv) episomal form of HPV-18 (SNU-1245). The promoter activity of HPV-URR was confirmed by transient transfection assay in C33A using the HPV-18 URR-CAT reporter plasmid.
RESULTS
Selective mutation was detected in TEF-1 (transcriptional enhancer factor) binding site in SNU-17, and the activity of URR in SNU-17 was higher than that of the prototype. The proliferation was more inhibited in SNU-17 by IFN-gamma (10 ng/ml) than in SNU-902, CaSki and HeLa. The increase of the HPV-URR activity might play a role in the inhibition of growth by interferon-g. The expression of HPV-16 E6/E7 were significantly decreased by ATRA or IFN-gamma.
CONCLUSION
Point mutation at TEF-1 binding site of SNU-17 was related with the increased transcriptional activity of URR. Mutation in the HPV-URR and alteration of HPV-URR activity in SNU-17 might be related with significant growth suppression by IFN-gamma.

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Case report

A Case of Triple-Alkylating Regimen and Peripheral Blood Stem Cell Transplantation for a Patient with Relapsed Ovarian Carcinoma: Jun Mo Lee, Seok Goo Cho, Jin No Park, Young Sun Hong, Hoon Kyo Kim, Sung Eun Namkoong, Kyung Shick Lee, Chun Choo Kim; J Korean Cancer Assoc. 2000;32(4):817-821.

Abstract PDF: Despite an aggressive surgical debulking followed by front-line chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in a subset of patients with hematologic malignancies and lymphoma with high-dose therapy (HDT) and hematopoietic stem cell transplantation, suggesting that this therapy may also be value in ovarian carcinoma. We report the successful outcome of HDT and peripheral blood stem cell transplantation (PBSCT) in a 41-year-old nulliparous woman who initially was diagnosed with advanced ovarian carcicnoma with FIGO stage IIIc. Her disease relapsed after 19 months from initial therapy of definitive surgery and intra- and post-operative chemotherapy. Subsequently, she received optimal debulking surgery and salvage chemotherapy followed by HDT with triple- alkylating regimen, composed of cyclophosphamide (100 mg/kg), thiotepa (500 mg/m2), and melphalan (100 mg/m2). Her pretranplant characteristics were platinum-sensitive and complete response state. She showed rapid hematologic recovery and mild regimen-related toxicity (Bear man's toxicity criteria), stomatitis (grade I), cardiac toxicitiy (grade II). She has been followed up for 36 months after the inital therapy and is doing well without relapse.

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Original Articles

Changes of Telomerase Activity by Protein Kinase C Modulators in Human Ovarian Cancer Cell Lines: Soo Young Hur, Joon Mo Lee, Sung Eun Namkoong, Jin Woo Kim; J Korean Cancer Assoc. 2000;32(4):724-733.

Abstract PDF: PURPOSE
This study was designed to find out whether protein kinase C (PKC) may affect telomerase activity in human ovarian cancers.
MATERIALS AND METHODS
To determine whether PKC modulators influence PKC activities, NIH: OVCAR-3 and CUMO-2, cells were treated with PKC inhibitors, G 6976 and bisindolyl maleimide I, and PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA). Telomerase acti vity was determined by telomeric repeat amplification protocol (TRAP). Analysis of the expres sion of each telomerase subunits, human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT), was performed by RT-PCR. We also examined the alternative splicing of hTERT.
RESULTS
G 6976 and bisindolylmaleimide I inhibited PKC activity. Telomerase activities appeared to be affected in a time-dependent manner by these two PKC inhibitors. PKC activities were increased in parallel with telomerase activity by TPA at the low dose (10 nM), but their activities were down-regulated at the high dose (1 micrometer). RT-PCR demonstrated the presence of hTR and hTERT mRNA before and after the treatment of PKC modulators, respectively, and showed the presence of one alternatively spliced transcript and full-length hTERT transcripts.
CONCLUSION
These results showed that telomerase activity was affected by PKC and suggested PKC modulation may serve as an useful tool in the regulation of telomerase activity.

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Development of a New Nonoclonal Antibody CC5 Using a Cervical Carcinoma Cell-line Derived From Korean Woman: Jin Woo Kim, Chun Ok Seo, Eun Young Cho, Heung Kee Kim, Sa Jin Kim, Soo Young Hur, Young Wook Kim, Tae Chul Park, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1999;31(3):562-574.

Abstract PDF: PURPOSE
Cancer of the uterine cervix remains the leading cause of cancer death in Korean women. Conventional examinations still have limitations with regards to sensitivity and specificity in diagnosis and to monitoring of the disease. Thus, an additional specific tumor marker is needed for early detection of recunence of uterine cervical carcinoma and for estimation of prognosis.
MATERIALS AND METHODS
Monoclonal antibodies against human cervical carcinoma were generated using hybridoma technology. These tnurine monoclonal antibodies were produced by fusion of spleen cells obtained from mice immunized with CUMC-6, a human cell line of squamous cell carcinoma derived from uterine cervix, and P3-X63-Ag8 mouse myeloma cells.
RESULTS
We obtained 415 hybridomas secreting specific monoclonal antibodies to cervical carcinoma antigen continuously. Among them, one hybridoma designated CCS that was highly reactive with cervical carcinoma was selected and examined on. the staining pattern and the reactivity with antigenic detenninants of cervical carcinoma. Immunohistochemical staining revealed that CCS monoclonal antibody reacted with all of the seven cervical carcinoma tissues, but also reacted with one of the ten (10%) normal cervical tissues. Westem blot analysis showed that CC5 monoclonal antibody detected single 19.5-kDa protein band in cervical cancer patient's sera. The detection rate was 88% (7/8). However, the antibody did not show any reactivity to 15 sera of normal healthy women tested. Sodium dodecyl sulfate polyacrylamide gel electrophoretic (SDS-PAGE) analysis of CCS monoclonal antibody immunoprecipitates of extracts of L-[S] methionine-labeled human cer vical carcinoma cells showed a major band in apparent molecular weight of 51,000 daltons. The isotype and subclass of CC5 monoclonal antibody was IgG2b in hemagglutination assay.
CONCLUSIONS
We have developed a new monoclonal antibody, CC5, against squamous cell carcinoma of the human uterine cervix. Further investigation is needed to establish this monoclonal antibody as an immunodiagnostic devise for cervical cancer.

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Integration of HPV and the Antibody Respones to HPV Proteins in Patients with Cervical Cancer: Joon Mo Lee, Seung Jo Kim, Jong Sup Park, Sung Eun Namkoong, Chan Joo Kim, Tae Chul Park, Soo Jong Um; J Korean Cancer Assoc. 1998;30(6):1184-1197.

Abstract PDF: PURPOSE
HPV (human papillomavirus) are known as the major causative agent for development of cervical cancer. High-risk HPVs, especially HPV-16 /18 DNA, are often found to be integrated into the human genome in high grade CINs as well as cervial cancer. Investigation of the relationship between the genomic states of HPV genes and their antibody response against the HPV-16 Ll/L2 virus-like particles (VLPs) and the in vitro translated E6 and E7 proteins may help to explain the mechanism of HPV-related cervical carcinogenesis and host immune responses.
MATERIALS AND METHODS
Cervical cancer tissues obtained from 41 patients with cervical cancer were studied by PCR, Southern blot hybridization and the antibody response against HPV-16 Ll/L2 VLPs and HPV-16 E6, E7 proteins of serum were tested by ELISA and radioimmunoprecipitation assay (RIPA), respectively.
RESULTS
Integrated forms of the HPV-16 DNA were found in 23 of the 38 patients (60.5%). The HPV-16 positive cervial cancer patients had a significantly higher prevalence (39.5%; 15/38) of antibodies to HPV-16 Ll/L2 VLPs than 8.7% (2/28) of the the control group (p<0.05). Antibodies to HPV-16 Ll/L2 VLPs were more detectable in 60% (9/15) of the cervical cancer patients with episomal forms of HPV-16 DNA than those who having only integrated HPV-16 (26.1%; 6/23) (p<0.05). Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38) of the patients with HPV-16 positive cervical cancer. And those were siginificantly higher than the positivities for the control group (8.3% and 2.8%), (p<0.05). The difference between seroreactivities to E6 and E7 proteins in the patients with episomal forms of HPV-16 DNA (pure episomal and mixed forms) and those with integrated froms of HPV-16 DNA was not significant (P>0.05). CONCLUSION: Integrated forms of HPV-16 DNA were prevalent in most patients with cervical cancer. Antibodies to HPV-16 Ll/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins appeared in the significantly larger proportions of the HPV-associated cervical cancer patients than in the controls. Antibodies to HPV-16 Ll/L2 VLPs were more detectable in the cervical cancer patients with episomal form of HPV-16 DNA than those who having only integrated forms of HPV-16. Antibody responses to HPV-16 E6 and E7 proteins were not influenced by the different viral states. More numbers of studies would be necessary to determine the relationship between the genomic states of HPV and the immune responses to their proteins by the such genomic and serologic parameters.

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The Effects of the Induction Chemotherapy on the Radical Radiotherapy in the Locally Advanced Cervical Cancer: Ki Mun Kang, Sei Chul Yoon, Hong Seok Jang, Mi Ryeong Ryu, Yeon Shil Kim, Sung Eun Namkoong, Seung Jo Kim; J Korean Cancer Assoc. 1998;30(4):762-771.

Abstract PDF: PURPOSE
We evaluated the prognostic factors, survivals and patterns of failure of the patients with locally advanced cervical cancer who received radical radiotherapy alone and induction chemotherapy followed by radiotherapy respectively.
MATERIALS AND METHODS
Between May 1985 to December 1992, one hundred and sixty three patients with locally advaneed cervical cancer received curative radiotherapy. Patients were divided into two groups: control group included 69 patients who received curative radiotherapy and combined group included 94 patients who received induction chemotherapy followed by curative radiotherapy. The curative radiotherapy consisted of external pelvic radiotherapy and intracavitary brachytherapy. Induction chemotherapy was delivered in VBP (vincristine, bleomycin, cisplatin) and FP (5-FU, cisplatin). Follow up period ranged from 2 months to 99 months with median of 50 months.
RESULTS
The overall response rate was 94.2% in the control group and 89.4% in the combined group. The response rate by control group was 66.7% for CR (complete response), 27.5% for PR (partial response), 5.8% for NR (no response). The response rate by combined group of CR, PR, NR were 64.9%, 24.5%, 10.6%, respectively. There was no difference in response for control group and combined group (p> 0.05). The 5-year overall survival had no significant difference in between control group and combined group (54.6% vs. 57.3%). The 5-year disease free survival also had no significant difference (52.9% vs. 55.0%). In the control group, 23 patients (33.3%) had treatment failure: twelve (17.4%) at a local recurrence, 9 (13.0%) as distant metastasis, and 2 (2.9%) with both local recurrence and distant metastasis. In the combined group, Thirty patients (31.9%) failed therapy, with local recurrence in 21 patients (22.3%), distant metastasis in 7 patients (7.5%), and both in 2 patients (2.1%). The difference between the two groups was not significant in view of patterns of failure. The major toxicities were nausea/ vomiting, leukopenia, anemia, and diarrhea. The prognostic factors affecting were hemoglobin level, KPS (karnofsky performance status), and treatment response in both group by multivariate analysis.
CONCLUSION
This study did not prove the efficacy of induction chemotherapy followed by radiotherapy in locally advanced cervical cancer.

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Glutathione S-Transferase Polymorphisms and Genetic Susceptibility to Cervical Cancer: Jin Woo Kim, Chun Geun Lee, Yeo Won Sohn, Hong Ki Min, Su Mi Han, Eun Young Cho, Kyung Sook Kim, Jin Woong Shin, Sa Jin Kim, Tae Chul Park, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1997;29(4):673-680.

Abstract PDF: PURPOSE
The identification of genetic traits that predispose individuals to environmentally induced cancers is one of the challanges in the assessment of individual cancer risk. The genetically determined differences in metabolism, related to glutathione S-transferases (GSTs) have been reported to be associated with various cancer susceptibility. The present study was set up to establish the frequencies of the polymorphic genotypes of two GST (GST- mu and GST-theta) isozymes in Korea, to evaluate a possible increased incidence of the genotypes associated with higher cervical cancer risks among Korean cervical cancer patients.
MATERIALS AND METHODS
In this study, extracted DNAs from cervical cancer patients (228 for GST-mu and 241 for GST-theta genotypes) and normal controls (360 for GST-mu and 353 for GST-theta genotypes) were analysed with the polymerase chain reaction (PCR).
RESULTS
The overall genotype distribution of the GST-theta polymorphisms was not statistically different between the patients and control groups. But, in the GST-mu null genotypes, there were remarkable differences between patients and control groups when the cervical cancer patients were devided into subgroups with respect to the age. The frequency of GST-mu null polymorphisms in the cervical cancer patients under the 40 years old was significantly higher compared to the patients above the 40 years old (0.01CONCLUSION
These results strongly suggest that individuals carrying GST-mu (null) alleles are genetically susceptible to cervical cancer which develops before 40 years of age and GST-mu null genotype may play a some role in cervical cancer progression.

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Cytochrome P450 2E1 Polymorphisms and Genetic Susceptibility to Cervical Cancer: Jin Woo Kim, Chun Geun Lee, Yeo Won Sohn, Hong Ki Min, Kyung Wook Lee, Ryung Joo Kwon, Hyun Sook Kho, Jin Woong Shin, Heung Kee Kim, Tae Eung Kim, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1997;29(3):429-436.

Abstract PDF: PURPOSE
Interindividual genetic differences in susceptibility to chemical carcinogens are one of the most important host factors in human cancer. The genetically determined differences in metabolism, related to cytochrome P450 (CYP450) genes have been reported to be associated with various cancer susceptibility. The present study was set up to establish the frequency of the polymorphic genotypes of two CYP450 (CYP2E1/PstI and CYP2E1/DraI) isozymes in Korea, to evaluate a possible increased incidence of the genotype associated with higher cervical cancer risks among Korean cervical cancer patients.
MATERIALS AND METHODS
In this study, extracted DNAs from 228 cervical cancer patients and 360 normal healthy controls were analysed with the polymerase chain reaction-restriction fragment length polymosphism (PCR-RFLP) method.
RESULTS
In the CYP 2E1 genotypes, detected by PstI or RsaI digestion, there were no statistically remarkable differences between the cervical cancer patients and control groups. And when the cervical cancer patients were divided into subgroups with respect to the age, the frequency of CYP 2E1/PstI polymorphisms in the cervical cancer patients under the 40 years old was not significantly higher compared to the controls or the patients above the 40 years old and, c1/c1 genotype was prominent in this type of polymorphism. The frequency of CYP 2E1/DraI polymorphisms in the cervical cancer patients was not significantly higher compared to the controls, and D/D genotype was prominent in this type of polymorphism. In cervical carcinoma, the polymorphic genotypes of CYP 2E1 were not correlated to other parameters including clinical stage, histological tumor type, and degree of differentiation.
CONCLUSION
These results suggest that individuals carrying CYP 2E1/PstI (c1/c1) or CYP 2E1/DraI (D/D) alleles are not genetically susceptible to cervical cancer in Korea.

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A Study on the Loss of Heterozygosity of the p53 Gene in Primary Uterine Cervical Carcinomas: Jin Woo Kim, Chun Geun Lee, Yeo Won Sohn, Hong Ki Min, Su Mi Han, Eun Young Cho, Kyung Sook Kim, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1997;29(2):280-290.

Abstract PDF: PURPOSE
Allelic deletion of p53 tumor suppressor gene have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. But the loss of heterozygosity (LOH) data on chromosome 17p are rare and controversial with respect to cervical carcinomas. So, we tried to elucidate the frequency of p53 locus LOH in primary cervical carcinoma and compared the LOH data with clinicopathological parameters.
MATERIALS AND METHODS
In order to detect LOH within one of the well-known tumor suppressor gene, p53, three intragenic polymorphisms (exon 1, exon 4, and intron 6) and one microsatellite distal to the p53 gene (D17S5) were examined. Paired DNA samples from 55 primary uterine cervical carcinomas and normal bloods were studied for the chromosomal allelic loss of p53 gene locus by polymerase chain reaction (PCR), the presence of human papilloma virus (HPV), and the presence of p53 gene point mutation by PCR-single conformation polymorphism (SSCP) analysis. And the relationships between allelic losses of this gene and conventional clinicopathological parameters were evaluated.
RESULTS
We could increase the heterozygosity of the p53 gene up to 1 (100%). The observed allelic loss rate of the p53 locus in informative cases was 5.5% (3/55) and the observed allelic loss rate of the D17S5 locus in informative cases was 8.7% (4/46) . Only one of the four patients with LOH at the D17S5 locus showed a concomittant allelic loss of the p53 gene. The overall LOH incidence of the chromosomal region comprising 17p13.1 (p53) to 17p13.3 (D13S5) was 10.9% (6/55). All the samples contained at least one of the oncogenic HPV type 16 and/or 18 sequences. No shifted bands were observed in the PCR-SSCP analysis of the p53 gene. The LOH of the p53 gene was not related to other parameters including clinical stage, histological type, and degree of differentiation.
CONCLUSION
Concerning with the results above, we conclude that the allelic imbalance of the p53 gene itself is not implicated as a major contributing factor in the malignant transformation or the tumor progression in HPV-positive cervical cancers. Another putative tumor suppressor gene which has more important function than p53 gene in cervical carcinogenesis might exist between these two loci [p53 (17p13.1) and D17S5 (17p13.3)].

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Expression of Gonadotropin-Releasing Hormone Receptor in Human Uterine Endometrial and Ovarian Tissues: Jin Woo Kim, Sung Eun Namkoong; J Korean Cancer Assoc. 1997;29(1):117-127.

Abstract PDF: PURPOSE
Gonadotropin-releasing hormone (Gn-RH) can cause regression of hormonedependent human tumors, including uterine endometrial and ovarian carcinomas. These effects were thought to be mediated through the inhibition of gonadotropic and steroid hormone from the hypothalamus. But, in addition to its classic hypophysiotropic action, Gn-RH might play a role as a modulator of activity in the brain and many peripheral organs. It has been reported that this analog has a direct inhibitory effect on the tumor and that the specific binding sites for Gn-RH were demonstrated in certain tumors responsive to Gn-RH. In support of a possible clinical use of Gn-RH analogs in the treatment of the endometrial and ovarian carcinomas, we tried to find out whether Gn-RH receptors are present on hormone dependent tumors.
MATERIALS AND METHODS
We have studied endometrial and ovarian tumor specimens and established uterine endometrial and ovarian carcinoma cell lines for the presence of Gn-RH receptor by the detection of its messenger ribonucleic acid (mRNA). We also compared the results obtained from tumor tissue specimens with the results from their corresponding normal tissues. Gn-RH receptor mRNA was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence.
RESULTS
Gn-RH receptor mRNA was detected in all normal endometrium and abnormally proliferative endometrium presenting dysfunctional bleeding, but not all in endometrial carcinomas (83%). Tumor stage and histologic grading had no relationship with receptor positivity. And, Gn-RH receptor mRNA was detected in less than 40% in normal myometrium and myomas. Gn-RH receptor expression was detected in same frequencies (86%) in normal ovarian tissues and ovarian carcinomas. Receptors were detected in a high proportion of the specimens from epithelial carcinomas (92%) and stromal tumors (100%) of the ovary. But, Gn-RH receptor was not detected in germ-cell derived tumors of the ovary. Established endometrial carcinoma (CUME-1) and epithelial ovarian carcinoma (CUMO-2) cell lines also demonstrated Gn-RH receptor mRNA, respectively.
CONCLUSIONS
The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of hormone-dependent normal tissues and their respective tumors, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in endometrial and ovarian malignancies.

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Prognosis of the small cell carcinoma of the uterine cervix:a comparative study: Yoo Mi Lee, Mi Ran Kim, Dae Young Jung, Sang Kyoon Han, Jong Sub Park, Sung Eun Namkoong, Seung Jo Kim, Hun Young Lee; J Korean Cancer Assoc. 1993;25(4):548-555.

Abstract PDF: No abstract available.

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Mutations of the p53 Tumor Suppressor Gene in Human Epithelial Overian Cancer: Jin Woo Kim, Dong Jin Kwon, Duk Jin Rha, Joon Mo Lee, Dae Hoon Kim, Sung Eun Namkoong, Seung Jo Kim; J Korean Cancer Assoc. 1994;26(2):296-304.

Abstract PDF: The p53 gene on chromosome 17p is considered to be a tumor suppressor gene, and frequent mutations in highly conserved regions of the p53 gene have been found in a wide variety of human cancers. Mutations in this portion of the gene are known to lead to the loss of the oncosuppressive potential of p53. To detect in a more sensitive manner p53 gene mutations in 28 human epithelial ovarian cancers we utilized the polymerase chain reaction-single strand conformation polymorphism(PCR- SSCP) technique. Using PCR primers for the regions of the p53 gene, including exons 4-9, p53 mutations were detected in 35.7%(10 of 28) of the ovarian cancers, Of the 10 mutations observed, 1 was found in exon 4, 7 were found in the region encompassing exons 5 and 6, 1 was found in exon 7 and 1 was found in the region encompassing exons 8 and 9. Mutations were clustered in exons 5 and 6 in highly conserved regions of the p53 gene. There results suggest that the mutations of the p53 gene play an important role in the development of human epthelial ovarian cancers.

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Inhibitory Effect of Transforming Growth Fasctor-β1 on Cellular Proliferation and c-myc Expression in Choriocarcinoma Cell Line: Sa Jin Kim, Jin Woo Kim, Jong Gu Rha, Guisera Lee, Seung Kyu Song, Sung Eun Namkoong; J Korean Cancer Assoc. 1995;27(6):961-968.

Abstract PDF: Modulation of cellular proliferation and c-myc oncogene expression after treatment of human choriocarcinoma cell line(BeWo) with trsnsorming growth factor-￥a1(TGF-￥a1) have been investigated by MTT [3-(4,5-dimethylthiaxol-2-yl)-2, 5-diphenyltetrazolium bromide] assay and Northern blotting analysis, respectively. TGF-￥a1 inhibited BeWo cell growth in a dose dependent manner at concentrations of 0.00110 ng/mL. When BeWo cells were exposed to 10 ng/ml of TGF-￥a1,c-myc was repressed after 4hr and completely aboiished at 24hr of stimulation. These results show that TGF-￥a1 may play an antiproliferative effect on BeWo cell growth via c-myc gene product. In vitro analysis of cellular and molecular alterations in BeWo cells in this study may aid in elucidating the mechanism of action of TGF-￥a1 on human choriocarcinoma tissues in vivo.

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Clinical Trial of Concomitant Thermo - Chemotherapy in Cervix Cancer Patients: Hong Seok Jang, Sei Chul Yoon, Su Mi Chung, Mi Ryeong Ryu, Yeon Shil Kim, Jong Sup Park, Sung Eun NamKoong, Seung Jo Kim, Kyung Sub Shinn; J Korean Cancer Assoc. 1995;27(6):968-978.

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A Study on the Loss of Heterozygosity of the Retinoblastoma Gene in Primary Uterine Cervical Carcinomas: Chun Geun Lee, Young Ju Choi, Hong Ki Min, Joo Ho Kim, Youl Hee Cho, Jin Woo Kim, Jae Hoon Kim, Tae Eung Kim, Jae Keun Jung, Sung Eun Namkoong; J Korean Cancer Assoc. 1996;28(3):502-512.

Abstract PDF: Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. In order to detect loss of heterozygosity(LOH) within one of the well-known tumor suppressor gene, Rb(retinoblastoma), in primary uterine cervical cancers, we analysed four polymorphic intronic sites of Rb locus using polymerase chain reaction(PCR) in 55 primary cervical cancer tissues. The estimated heterozygote frequencies of intronl/BamHI, intronl7/XbaI, intron25/DraI, and intron 20 variable number of tandem repeat(VNTR) regions were 49%, 49%, 42%, and 80%, respectively. The observed frequencies of tumors with LOH at each locus were 21%(5 /24), 17%(5/29), 20%(5/20) and 44%(7/44) for intronl/BamHI, intronl7/XbaI, intron25/DraI and intron 20 VNTR polymorphic loci, respectively. The overall frequency of cervical cancer with at least one LOH at the Rb locus in this study was 14%(7/49), indicating that LOH at the Rb locus was not necessarily associated with cervical carcinogenesis. All the tumors showing LOH at the Rb locus were histologically moderatelv to poorly differentiated types and most of them(5 of the 7, 71%) were over FIGO stage II. These results suggest that the tumors with LOH at this locus may represent the general genomic instability which will contribute to the tumor progression and LOH of this gene may be used as one of the prognostic factors in cervical cancer in the future.

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